Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS

ARDS, Human Clinical Trial

— EXIT-ARDS  

Official title:

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Acute Respiratory Distress Syndrome: A Phase I/II Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05127122
• Other study ID #: DB-EF-EXITARDS-0003
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2024
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Direct Biologics, LLC
• Contact: Bill Arana
• Phone: 1-800-791-1021
• Email: clinicalaffairs[@]directbiologics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and efficacy of intravenous(IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles(EV), ExoFlo, as treatment for Acute Respiratory Distress Syndrome.

Description:

To evaluate the safety and efficacy of intravenous(IV) administration of bone marrow mesenchymal stem cell-derived extracellular vesicles (EV), ExoFlo, as treatment for Acute Respiratory Distress Syndrome. ExoFlo is also referred to as Investigational Product (IP) throughout the protocol. The duration of the study is 60 days, and the endpoints are as follows: Primary Endpoint: 1. The incidence of serious adverse events. 2. All-Cause Mortality at 28 days. Secondary Endpoints: 1. Ventilator-free days at 28days. 2. Improvement in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio from pre-infusion baseline(Day 0)to Day 7. The study population will consist of 81 inpatient adult patients between 18 and 85 years of age with moderate to severe ARDS as defined by modified Berlin's criteria. Patients will be randomized via Interactive Response Technology to one of the following 3 treatment arms: 1. PLACEBO: Normal saline 100 mL 2. EXPERIMENTAL: IP 10 mL mixed with Normal Saline 90 mL 3. EXPERIMENTAL: IP 15 mL mixed with Normal Saline 85 mL

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 81
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female aged 18-85.

4. Moderate to severe ARDS as defined by modified Berlin definition (See Section 2.2.1), which includes timing within 1 week of known clinical insult or new or worsening respiratory symptoms; bilateral opacities not fully explained by effusions, or lung collapse; respiratory failure not fully explained by cardiac failure or fluid overload; PaO2/FiO2 = 200 mm Hg.

5. Hypoxia requiring noninvasive oxygen support such as Nasal Cannula (NC), Nonrebreather (NRB), Bilevel Positive Airway Pressure (BIPAP), Continuous Positive Airway Pressure (CPAP), high flow nasal cannula oxygen (HFNC O2) or mechanical ventilation (MV) despite initiating standard of care.

6. If the candidate is either a male or female of reproductive potential, he or she must agree to use of double barrier method of highly effective birth control contraception such as condoms with oral contraceptive pill or choose to remain abstinent if already practicing abstinence during the screening period. The required duration of usage of double barrier method OR maintenance of abstinence must include the time from the beginning of the screening period until 90 days following the last dose of the study treatment.

Exclusion Criteria:

1. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.

2. Active malignancy requiring treatment within the last five years.

3. Major physical trauma in the last 2 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries, such that not one or more injury may be undiagnosed at time of screening.

4. Diagnosis or suspected diagnosis of sepsis without basic microbiology cultures (urinalysis, urine culture, two sets of blood cultures, respiratory culture, at least a standard respiratory viral panel PCR) being collected prior to screening. (Note: Standard respiratory viral panel is defined by at least PCR testing for Adenovirus, Influenza A, Influenza B, Parainfluenza 1-3, Rhinovirus/Enterovirus, and RSV.)

5. Duration of mechanical ventilation exceeds 5 days or 120 hours.

6. Severe pre-existing organ dysfunction prior to admission, as evidenced by being currently listed on one or more organ transplant list, or intermittent Hemodialysis (HD) or Peritoneal Dialysis.

7. Presence of severe hematologic disorder or coagulopathy, such as Disseminated Intravascular Coagulopathy, as evidenced by the activation of a Massive Transfusion Protocols (as defined by the rapid administration of packed Red Blood Cells, Fresh Frozen Plasma and Platelets in fixed ratios, including at least 6 packed Red Blood Cells, within a 24 hour period) within 72 hours or frequent thrombosis of catheters (as specified by replacing 2 catheters or more within a 72 hour period of new placement) within 72 hours.

8. Severe anemia or myelodysplastic syndrome requiring more than 10 units of packed Red Blood Cells transfused within the last 12 months.

9. Patient is currently connected to Extracorporal Membrane Oxygenation.

Related Conditions & MeSH terms

• ARDS, Human
• Respiratory Distress Syndrome

Intervention

Drug:
• Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles
Injectable

Other:
• Saline
Placebo Saline

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Direct Biologics, LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of serious adverse events.		60 days
Primary	Number to patients with All-Cause Mortality at 28 days		28 days
Secondary	Ventilator-free days at 28days		28 days
Secondary	Change in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio from pre-infusion baseline(Day 0)to Day 7.PaO2 may be calculated from arterial blood gas (ABG)or imputed from the SpO2daily.		7 days